Subchronic metformin pretreatment enhances novel object recognition memory task in forebrain ischemia: behavioural, molecular, and electrophysiological studies

Ghorbangol Ashabi,1,* Leila khalaj,2 Alireza sarkaki,3

1. Tehran University of Medical Sciences, Tehran
2. Rasht University of Medical Sciences
3. Ahvaz University of Medical Sciences

Abstract


Introduction

Metformin exerts its effect via amp-activated protein kinase (ampk), which is a key sensor for energy homeostasis that regulates different intracellular pathways. metformin attenuates oxidative stress and cognitive impairment.

Methods

In our experiment, rats were divided into 8 groups; some were pretreated with metformin (met, 200 mg/kg) and (or) the ampk inhibitor compound c (cc) for 14 days. on day 14, rats underwent transient forebrain global ischemia.

Results

data indicated that pretreatment of ischemic rats with metformin reduced working memory deficits in a novel object recognition test compared to group with ischemia– reperfusion (i–r) (p < 0.01). pretreatment of the i–r animals with metformin increased phosphorylated cyclic-amp response element-binding protein (pcreb) and c-fos levels compared to the i–r group (p < 0.001 for both). the level of creb and c-fos was significantly lower in ischemic rats pretreated with met + cc compared to the met + i–r group. field excitatory postsynaptic potential (fepsp) amplitude and slope was significantly lower in the i–r group compared to the sham operation group (p < 0.001). data showed that fepsp amplitude and slope was significantly higher in the met + i–r group compared to the i–r group (p < 0.001). treatment of ischemic animals with met + cc increased fepsp amplitude and slope compared to the met + i–r group (p < 0.01).

Conclusion

We unravelled new aspects of the protective role of ampk activation by metformin, further emphasizing the potency of metformin pretreatment against cerebral ischemia.

Keywords

Global cerebral ischemia, metformin, ampk, memory and learning, creb